Use of Pyridostigmine for Constipation in Diabetics

Inclusion Criteria:

• Subjects with diabetes mellitus (Type I or type II), diagnosed by a physician.

• On medical treatment for diabetes (oral medication or injected insulin) for at leastone year

• Symptomatic constipation at least 25% of the time in the past year (Rome II criteriafor functional constipation)

• 18-70 years of age

• Colonoscopy negative for obstructive lesions, cancer, or inflammatory bowel disease (IBS) within the last 8 years if 50 years of age or older

• Able to provide written informed consent before participating in trial

• Able to communicate adequately with the Investigator and to comply with therequirements for the entire study

Exclusion Criteria:

• History of pelvic floor dysfunction (other functional GI disorders, eg IBS, non-ulcerdyspepsia are acceptable); Specifically, patients will be excluded if they have atleast 2 of the following 3 criteria:

• History of digital evacuation of the rectum or pressure on the posterior aspectof the vagina or perineum to facilitate defecation

• Examination findings suggestive of puborectalis spasm or anismus, on assessmentby an experienced gastroenterologist with expertise in this field; i.e. high analsphincter tone at rest, failure of perineal descent by >1cm on straining, andtenderness or paradoxical contraction of the puborectalis on digital examination

• Requirement of > 200g to expel a rectal balloon during voluntary straining

• Abdominal surgery other than appendectomy, cholecystectomy, hysterectomy, tuballigation, or inguinal hernia repair

• Suspected or known gastrointestinal or genitourinary obstruction

• Uncontrolled hypertension (defined as > 150/90 at rest)

• Known cardiac arrhythmia or ECG abnormalities, i.e. cardiac conduction disturbances (2nd or 3rd degree atrioventricular (AV) block, prolonged corrected QT interval (QTc)(> 460 msec) or bradycardia (< 45 beats/minute))

• Renal insufficiency with serum creatinine greater than 2 mg/dl based on a reading fromthe previous 6 months

• Asthma or chronic obstructive pulmonary disease requiring systemic steroids in theprevious 3 years (inhaled steroids acceptable)

• Current use of narcotics, gut prokinetic drugs (eg metoclopramide, domperidone,tegaserod, senekot), anticholinergic medication (eg. Hyoscyamine, belladonna),antidiarrheals (Imodium, Lomotil), or laxatives other than fiber supplements,docusate, or glycerin suppositories. Patients on any of these restricted medicationsmust cease use at least 48 hours before starting and for the duration of both studyphases. No rescue laxatives will be permitted within 7 days of transit testing

• Patients who have taken any investigational medications within the past 30 days

• Known intolerance or allergy to eggs

• Pregnant or breast-feeding females